Method for making 5-chloro-omicron-cresol and 4, 5-dichloro-omicron-cresol



Jan. 22, 1957 Bl-:MAN ET AL AND 4.5-DICHLORO-O-CRESOL Filed April 26, 1954 rom in arl/o n 6-6/2/ofo-o-creso/ 1N V EN TORS F/oga/L. Bem an HY @mafm @TTOR/VEYS United States Patent O M' METHOD FOR MAKING 5CHLOR00CRESOE AND 4,5-DICHLORO--CRESOL Floyd L. Bernau and Andrew J. Dietzler, Midland, Mich., assignors to The Dow Chemical7 Company, Midland, Mich., a corporation of Delaware Application April 26, 1954, Serial No. 425,752

8 Claims. (Cl. 2641-623) This invention pertains to a new and improved method. for the preparation of -chloro-o-cresol and 4,5-dichloroo-cresol from p-chlorotoluene whereby substantially pure products can readily be obtained.

' By S-chloro-o-cresol is meant S-ChlorO-Zmethylphenol, and by 4,5-dichloro-o-cresol is meant 4,5-dichloro-Z-methylphenol, the substituents` in the benzene ring. being numbered starting with the hydroxyl group. as l and proceeding toward the methyl group as-2.4

The preparation of a chloropheno'lic compound by, direct chlorination of the parent phenolic-compoundusually resultsin the formation of a mixture comprising undesired products havingmore and/ or less than the desired degree of chlorination and also comprising position isomers. of. the desired product. The separation of such a. mixture is often difiicult'and sometimes .only poor yields. ofthe desired product arenobtained. The directchlorinaf tionmethod is particularly inappropriate whenthey chlorol substituent in the desired. product occupies. a position.. meta; to the. phenolic hydroxyl group,4 as it"doesfinA 5-.chloro-o-cresol and in 4,5-dichlorolo-cresol. The' direct.

mono-chlorination of ocresol leadsr to a. mixturopredominating in 4- and 6fchloro-o-cresols, and the dichlorination leads Yto \4,6'diehloroccresol; very little, lif any, of. the Sech'loro-o-cresol--orn 4,S-dichloro-o-cresolv beingf obtained.

lt hasalso been proposed 'to `prepare chloro-cresolsibyhydrolysis of one. ofthe chloro-substituents of avpoly chlorotoluene. However, the mono-hydrolysis vofiapolyi chlorotoluene is not-selectivey and mixtures of chlorocresolsarevobtainelg Themethod is. not adapted-;forf makingpure; 5-chloro-o-cresol or 4,5-dichloro--o,- c1 e,sc,)l.y

Theknown methods4 for. preparation of; Schloro-o.- cresol'and -of 4,5-dichloro-o-cresol are by' indirectprocev d ure. For. example, the preparation-of 5-eh lo roo.cresol has.v been. effectedA by the acid-catalyzed `deconipositionof'- 5-chlorfof2-me,thylbenzenediazoniurny saltthe latter havingbeen made by diazotization-of.5chlorooftoluidine which had, been; madeby reduction of -f-l-chlorofZinitroV toluene.v The last named material is'not a readilyavail-- able. starting'material andthe necessary ysequence of reac+ tions .is tedious and expensive.. Such a process does. not lend: itself to commerciali production. i lt. is an object of. thisinvention to-provide'a newand improved method for making 5-ch1oroocres4oltand/ or 4,5;-dichl'oro-o-cresol. A further objectfistoprovideqsuoh a method for making.5-chloro-o-cresol Aa nd/or4,5'fdichloro-ocresolvfrom readily available starting materials. A specific object is to providesuch a method; for making 5-chl'oro-o-cresoll and/or 4,5-dichloro-o-creso1 from.-;p chlorotoluene.- Another object is to provide such: a method which' is readily adaptable-to commercialpro duction. Other objectsY and advantages vwill beevident from the following description of the invention. I Theobjects'; of this invention are attained; in a new and improved method for making S-chlo'ro-'o-cresol gand/ or ll-dichloro-o-cresol from p-chlorotoluene, which method 2,778,857 Patented Jan. 22, l 957 ICC comprises steps, hereinafter more completely described, which involve the following chemical reactions:

p-Chlorotoluen'e is brominated, whereby 2bromo`4 chlorotolu'ene is produced;v

2-b'rom`o-4-chlorotolu'ene is hydrolyzed', whereby' 5- chl'oro-oc'resol is produced;

5-chloroocresol is chlorinated, whereby 4,5-dichlor'o'- o-cresol is produced.

TheV drawing is a diagrammatic ow sheet showirigi the steps of' this process. v By such method, 5chloroocresol and/ or 4,5-di'chloroocresol can be obtained in good yield and of good quality' from readily available starting materials. The end' pro'ducts and" intermediate products are readily separated from` their synthesis reaction mixtures', and recovered starting materials can4 be utilized in'succeieding runs'. Tli'epro'ces's i'sreadily adapted to commercialoperation.

In the first step of the process whereby 5chloro -o cresol and/or 4,5-dich'loro-o-cresol is prepared fromV p'- chlorotoluene, the latter compound is brominated to" pro'- du'ce 2'bromo4'chlorotoluene. i

of a carrier catalyst, e. g. 0.5y to 2 percent byweight, based' on'. the. p-chlorotoluene, of ferrie chloride, alur'nif n uni ch1oride, antimony'pentachloride, the aluminum# mercury couple or iodine.' Thev temperature; should b'e' controlled below about 5 0 .C preferably from' 0 CQ to 30 C. The bromine 'preferably' added gradually so as to avoid. a high Concentration of. freebromine 1n th` reaction" mixture and usually. the amount. of bro ne charged" is less than that theoretically/'j required' for rea tion onan equimolecular basis with. the pchlorot'olii ne' charge. For example, 0.5 to 0.9l molecular proportion ofbiomine is usually charged forA each molecular' pro` portion of p-chlorotoluene. After completion of 'fthe bromination reaction, the reaction mixtureislprjeferably washeidwith water to extract andremove thecatalystand ispreferablytreated with alkali; eygi washed withsodiuir'l' hydroxide solution, to' remove acidic'material's sufcli'as hydrogen bromide. From the neutralreaction" product, unreaeted'p-chlorotoluene and the 2lbromo-4 -'chloroto1i-' enoproduct can be separatede g. by 'fr`actionaldistilla a solution comprising water, an alcohol, e. g. methanol v or.' ,glycolgasthey mutual solvent, andan excess of L an alkalime'ta'l hydroxide such as sodium "hydroxide'or pjotas: sium hydroxide, and the liquid mixture is heatedin'a' closedvessel, with.. agitation, under a pressurevat least as great as the autogenous pressure, to a temperature betwee'nflZS vandf240P' C., preferably betweenf1709`and 220' C.v Us'ually'from about'2 'toabout Smolecular proportions V'offalkali are employed per molecular proporr tion of'i2lbrorno4chlorotoluene. Anyalkali metal hye droxide, i. e., a hydroxide of lithium-sodium, potassium; rubidium'orcaesium, or alkaline earth metaloxide ory hydroxide', i. e. an oxide orfhydroxiderof n'fiagnesium,l calcium; barium or strontium, can be used. Thelcon-y centration of alkali Ais notl critical, but isE usually from A suitable procedure is; to add bromine to' liquid p-chlorotoluene' in the presence 3 about to about 30 percent by weight of the aqueous medium. The proportion of mutual solvent is not critical, but is usually from about 5 to about 90 percent by weight of the aqueous alkali mixture. The reaction is continued until a substantial proportion of the Z-bromo-4-chlorotolene has been hydrolyzed, as shown by analysis of a sample portion, e. g. by titration, usually for 2-30 hours.

The hydrolysis reaction mixture can be treated to recover unreacted 2-bromo-4-chlorotoluene and to collect the 5chloroocresol product. For example, the reaction mixture resulting from the hydrolysis of 2-bromo-4- chlorotoluene with aqueous alkali in methanol solvent can be distilled to remove the methanol while adding water to the residue if necessary to keep the alkali and alkali salt of the cresol product in solution. After the methanol has been removed, the unreacted 2-bromo-4-chlorotoluene separates as a layer substantially insoluble in the aqueous alkali solution of the cresol hydrolysis product. The layers can be separated and traces of 2-bromo-4-chlorotoluene can be removed from the aqueous alkali solution of the cresol by `extraction or by steam distillation, if desired. The aqueous alkaline solution can then be acidicd and cooled whereupon the 5-chloro-o-cresol precipitates and usually crystallizes and can be separated, washed, dried and recrystallized if desired. l

It is surprising that the hydrolysis of 2bromo4chloro toluene, under the conditions as described above, occurs almost exclusively and selectively on the 2-bromosubstituent, only a negligible amount of hydrolysis occurring on the 4chlorosubstituent. A consequence of such highly selective hydrolysis is that 5-chloro-o-cresol, which is diicult to obtain by previously known methods, can now be readily obtained from an available starting material in good yields, and in a pure state, being substantially free ot' isomeric chlorocresols.

In the preparation of 4,5-dichloro-o-cresol from p-chlorotoluene according to the method of this invention,5-chloro-ocresol, made as described hereinbefore, is chlorinated. The 5-chloro-o-cresol can be dissolved in a suitable chlorination solvent, e. g. chloroform, carbontetrachloride or acetic acid, and chlorine passed into the solution with stirring, usually at a temperature of C. to 80 C., preferably between about 20 and about 50 C., until a quantity of chlorine has been added approaching that theoretically equivalent on a molecular basis to the 5-ch1oro-o-cresol charge. After the complete addition of chlorine, the solvent can be removed by distillation, and the residue is crude 4,5-dichloro-o-cresol which usually crystallizes on cooling. The crude product can be fractionally distilled, preferably under reduced pressure, and/ or recrystallized to eect a further purification if desired.

Surprisingly, the chlorination of S-chloro-o-cresol as just described takes place almost exclusively on the nuclear position para to the cresolc hydroxyl group. Very little, if any, chlorination of 5-chloro-o-cresol occurs on other nuclear positions. The consequence of such selectivity is that 4,5-dichloro-o-cresol, which is difficult to obtain by hitherto known methods, can now be readily obtained by the method of this invention.

The following. examples, taken together, illustrate the invention, butshould not be construed as limiting its scope.

Example l.-Bromnaton of p-chlorotoluene Into a reactor equipped with a stirrer, reflux condenser, thermometer, dropping funnel and an external cooling bath, were charged 3968 grams of p-chlorotoluene and 39.7 grams of ferrie chloride catalyst. The mixture was cooled and, with stirring, 4380 grams of bromine was dropped in over a period of about 26 hours, during which the temperature of the reaction mixture was maintained below 9 C., generally between 2 and 4 C. After the bromine addition, the reaction mixture was washed in a separatory funnel with 2 liters of water, then with 2 liters of aqueous 1.9 percent sodium hydroxide solution and again with 2 liters of water. The weight of the crude product was 6004 grams.

The washed crude bromination product was fractionally distilled under a reduced pressure, whereby lowerboiling materials, principally unreacted p-chlorotoluene, were collected up to a distillation temperature of C. at 25 mm. mercury absolute pressure and weighed 899 grams.

The principal distillate, substantially 2-bromo-4-chl0rotoluene, was collected at distillation temperatures between 110 and 115 C. under 25 mm. of mercury absolute pressure and weighed 4211 grams.

Into an iron autoclave were charged 117 grams (0.57 gram-mole) of 2-bromo-4-chlorotoluene, prepared in the manner described above in Example l, 120 mls. of water, 680 mls. of methanol and 80 grams (2 gram-moles) of sodium hydroxide. The autoclave was closed, and the reaction mixture was heated to, and maintained at, temperatures between and 180 C. for 25.5 hours, with agitation. After the hydrolysis reaction, the methanol was distilled out of the reaction mixture and the aqueous residue was cooled, whereupon the unreacted 2-bromo- 4-chlorotoluene separated. The recovered 2bromo4 chlorotoluene fraction amounted to 57.6 grams. The aqueous alkali layer was steam distilled to remove traces of 2-bromo-4-chlorotoluene, cooled to 20 C. and acidiiied with concentrated hydrochloric acid to pH 1. 5-chloro-ocresol crystallized out, was collected, washed with water and dried to yield 29.7 grams of product melting at a temperature of 56-61 C. The yield of 5-chloro-o-cresol corresponded to about 72 percent, based on the amount of 2-bromo-4-chlorotoluene which was consumed. Analysis of the aqueous alkali salt hydrolysis liquor showed the presence of 0.265 gram-equivalent of bromide ion and 0.027 gram-equivalent of chloride ion, giving evidence that only a small proportion of the hydrolysis had involved a chloro-substituent.

Example 3.-Hydrolyss of 2brom0-4chlorotoluene Into a copper autoclave were charged 117 grams (0.57 gram-mole) of 2-bromo-4-chlorotoluene, prepared in the manner described in Example 1, 120 mls. of water, 680 mls. of methanol and 80 grams (2 gram-moles) of sodium hydroxide. The autoclave was closed and the reaction mixture was heated at a temperature of 200 C. for 2Vz hours, with agitation. After the hydrolysis reaction, analysis showed the presence of 0.456 gram-equivalent of bromide ion and 0.02 gram-equivalent of chloride ion. The methanol was distilled out of the reaction mixture and the aqueous residue was cooled, whereupon the unreacted 2-bromo-4-chlorotoluene separated. The recovered 2-bromo-4-chlorotoluene fraction amounted to 14.5 grams, or 12.4 percent of the amount thereof linitially charged. The aqueous alkali layer was steam distilled to remove traces of 2-bromo-4-chlorotoluene, cooled to 20 C. and acidiied with concentrated hydrochloric acid to pH 1. 5-chloro-o-cresol crystallized out, was collected, washed with water and dried to yield 50.0 grams of product melting at a temperature of 59-60 C. The yield of 5-chloro-o-cresol obtained corresponded to about 76.7 percent of theoretical, based on the amount of 2-bromo- 4-ch1orotoluene which was hydrolyzed.

Example 4,-Chlorination of 5-chloro-a-cresol Into a solution of 21.4 grams (0.15 gram-mole) of 5chloroo-cresol (prepared in the manner described in Examples 2 and 3) dissolved in 190 mls. of chloroform, was passed 10 grams (0.14 gram-mole) of chlorine over a period of about 30 minutes, during which the temperature was maintained at about 18-45 C. After the chlorine addition, the chloroform was distilled off under atmospheric pressure to a residue temperature of about 90 C. The residue was cooled to 30 C. and seeded,

whereupon the entire residue crystallized. The yield of crude 4,5-dichloro-o-cresol was 89 percent of theoretical.

We claim:

1. In a method for making a chloro-o-cresol having a chlorine atom in the -position of the molecule, the step of making 5-chloro-o-cresol by hydrolyzing 2-bromo-4- chlorotoluene by heating a liquidvmixture of 2-bromo- 4-chlorotoluene and a molecular excess of an aqueous alkali under a pressure at least as great as the autogenous pressure at a hydrolyzing temperature between 125 and 240 C.

2. In a method according to claim 1, the step of heating a liquid mixture of 2-bromo-4-chlorotoluene, a molecular excess of an alkali metal hydroxide, water and methanol under a pressure at least as great as the autogenous pressure at a hydrolyzing temperature between 170 and 220 C.

3. A method for making 5chloroocresol which com prises heating a liquid mixture of 2-bromo-4-chloro toluene and a molecular excess of aqueous alkali at a hydrolysis temperature between 125 and 240 C.

4. A method according to claim 3 wherein the alkali is an alkali metal hydroxide.

5. A method according to claim 3 wherein the alkali is sodium hydroxide.

6. A method for making 5ch1oroocresol which comprises heating a liquid mixture of 2-bromo-4-chlorotoluene, a molecular excess of an alkali metal hydroxide, water and methanol at a hydrolysis temperature between 170 and 220 C.

7. A method according to claim 6 wherein the alkali metal hydroxide is sodium hydroxide.

8. A method for making 5-chloro-o-creso1 which comprises preparing a liquid mixture of 2brorno4chloro toluene and an aqueous alkali solution, which aqueous alkali solution contains water, methanol in amount corresponding to from about 5 to about 50 percent by weight Vof the aqueous alkali solution, and sodium hydroxide in References Cited in the tile of this patent UNITED STATES PATENTS Britton et al Nov. 7, 1933 Jacobi et al Mar. 26, 1935 OTHER REFERENCES Ullmann et al.: Chem. Abstracts, vol. 1 (1906), page 436.

Cohen et al.: Jour. Chem. Soc. (London), vol. (1914), pages 1910, 1912.

Zincke et al.: Annalen der Chemie (Liebig), vol. 417 (1918), page 207. Abstracted in Chem. Abstracts, vol. 13 (1919), pp. 1830-1. 

3. A METHOD FOR MAKING 5-CHLORO-O-CRESOL WHICH COMPRISES HAVING A LIQUID MIXTURE OF 2-BROMO-4-CHLOROTOLUENE AND A MOLECULAR EXCESS OF AQUEOUS ALKALI AT A HYDROLYSIS TEMPERATURE BETWEEN 125* AND 240*C. 